rs17494540

chr7-136879585-T-Cchr7-136879585-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001006630.2(CHRM2):c.-125+10167T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 151,922 control chromosomes in the GnomAD database, including 1,585 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1585 hom., cov: 32)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.30

Genes affected

CHRM2 (HGNC:1951): (cholinergic receptor muscarinic 2) The muscarinic cholinergic receptors belong to a larger family of G protein-coupled receptors. The functional diversity of these receptors is defined by the binding of acetylcholine to these receptors and includes cellular responses such as adenylate cyclase inhibition, phosphoinositide degeneration, and potassium channel mediation. Muscarinic receptors influence many effects of acetylcholine in the central and peripheral nervous system. The muscarinic cholinergic receptor 2 is involved in mediation of bradycardia and a decrease in cardiac contractility. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM2	NM_001006630.2	c.-125+10167T>C		intron_variant		ENST00000680005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM2	ENST00000680005.1	c.-125+10167T>C		intron_variant			NM_001006630.2	P1
	ENST00000586239.5	n.274-93694A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20650 AN: 151804 Hom.: 1587 Cov.: 32

Gnomad AFR AF: 0.0860

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.0824

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.134

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.136 AC: 20638 AN: 151922 Hom.: 1585 Cov.: 32 AF XY: 0.132 AC XY: 9783 AN XY: 74288

Gnomad4 AFR AF: 0.0858

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.00985

Gnomad4 SAS AF: 0.0816

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.132

Alfa AF: 0.0656 Hom.: 108

Bravo AF: 0.130

Asia WGS AF: 0.0440 AC: 154 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
Cadd	Benign	19
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17494540; hg19: chr7-136564332;